Studies have continued to determine the molecular and cellular targets of estrogenic chemicals and establish the mechanisms by which interactions of estrogens with developing genital tract target cells result in permanently altered differentiation, including dysmorphology and neoplasia. In the period covered by the report, the developmentally estrogenized mouse model has continued to be used to understand both the development of the mammalian genital tract as well as the mechanisms underlying hormonally-associated cancers. In addition to neoplasia in the female structures derived from the Mullerian duct (e.g., uterus), cancers associated with these same embryonic derivatives developed in the prostates of male mice. The ontogeny and tissue specificity of estrogen and androgen metabolism was also studied in the male genital tract. The developing Mullerian duct has been further studied at the cellular and molecular levels. It was determined that the immature mouse uterus, which is an especially sensitive tissue for estrogen-induced cancers, had abundant estrogen receptors (ER) in the underlying stroma, while the epithelium was relatively efficient in detectable ER. This raises the possibility that ER deficient cells may be those which are most susceptible to neoplastic transformation. These same cells however, contain receptors for at least two growth factors--EGF and IGF-1. The immature uterus proliferates in vivo in response to EGF implants suggesting a role for these growth factors. We also recently demonstrated the expression of the mRNA for a uterine secretory protein in the seminal vesicle of developmentally-estrogenized male mice, the first example of pseudo-hermaphroditism at the molecular level. Studies on the metabolism of estrogens to reactive forms have shown that the mouse uterus forms catechol estrogens and that the enzyme responsible for their inactivation is relatively low. This provides a mechanism for generation of reactive estrogenic metabolites close to the target cell.